Mechanisms of Functional Axon Regeneration

功能性轴突再生机制

基本信息

批准号：
10558455
负责人：
Alexandra Byrne
金额：
$ 36.64万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10558455
关键词：
Adenosine Diphosphate Ribose Adult Affect Age Animals Apoptosis Axon Axotomy Behavioral Assay Biological Assay Caenorhabditis elegans Cell Communication Cells Central Nervous System Chemicals Clinical DNA Repair Development Disease Distant Enhancers Exposure to Functional Regeneration Genes Genetic Screening Genetic Transcription Genome Goals Image Individual Injury Knowledge Lasers Location Mammals Mitosis Modeling Modification Molecular Motor Movement Mus Mutagenesis Mutate Mutation Natural regeneration Nervous System Nervous System Trauma Neurobiology Neuronal Injury Neurons PARP inhibition Poly(ADP-ribose) Polymerase Inhibitor Poly(ADP-ribose) Polymerases Process Proteins Recovery Recovery of Function Regenerative response Resolution Role Site Synapses Synaptic Vesicles Testing Time Tissues Visualization axon growth axon injury axon regeneration chemical genetics chromatin modification design experience functional restoration gamma-Aminobutyric Acid gene conservation genetic analysis improved in vivo inhibitor injured injury and repair injury recovery knock-down mutant nerve injury optogenetics pharmacologic prevent regeneration function reinnervation repaired response to injury small hairpin RNA synaptic function synaptogenesis

项目摘要

A fundamental question in neurobiology is how axons respond to injury and disease. Damaged neurons can sometimes repair themselves by a process called axon regeneration. However, many neurons do not regenerate, often resulting in permanent deficits following nerve injury. Clinical strategies to repair the injured nervous system are lacking because the mechanisms that determine whether an injured axon will functionally regenerate are poorly understood. Therefore, determining the mechanisms that regulate individual components of the regeneration response, including those that determine whether an injured axon will regenerate and whether it will reform functional synapses (functional axon regeneration), is critical to understanding how to improve functional recovery after injury. To reach this goal we are investigating how a number of genes that we recently identified as regulators of functional axon regeneration determine whether an injured axon will we repaired. Our approach is to take advantage of the powerful C. elegans model of axon regeneration, which has a highly conserved genome, is genetically tractable, and in which functional axon regeneration can be studied in vivo and with single axon resolution, to perform detailed genetic analyses, laser axotomy, imaging, and behavioral assays. Answering the above questions is essential to our understanding of functional axon regeneration in the adult nervous system and will significantly enhance our understanding of how to elicit regeneration and restore function to damaged neurons.

神经生物学的一个基本问题是轴突如何响应损伤和疾病。受损的神经元可以有时通过称为轴突再生的过程进行自我修复。然而，许多神经元并不再生，通常会导致神经损伤后出现永久性缺陷。修复受伤者的临床策略神经系统缺乏，因为决定受损轴突是否发挥功能的机制再生的了解甚少。因此，确定调节各个成分的机制再生反应，包括决定受伤的轴突是否会再生的反应以及它是否会改革功能性突触（功能性轴突再生），对于理解如何改善受伤后的功能恢复。为了实现这一目标，我们正在研究我们的一些基因如何最近被确定为功能性轴突再生的调节因子，决定了受损的轴突是否会被我们修复了。我们的方法是利用强大的线虫轴突再生模型，该模型具有高度保守的基因组，在遗传上易于处理，并且可以研究功能性轴突再生体内和单轴突分辨率，以进行详细的遗传分析、激光轴切术、成像和行为分析。回答上述问题对于我们理解功能轴突至关重要成人神经系统的再生，并将显着增强我们对如何引发的理解再生并恢复受损神经元的功能。